Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development.
Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development.
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DOI:
10.1016/j.neuron.2010.01.007
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发表时间:
2010-02-11
期刊:
影响因子:
16.2
通讯作者:
Brose, Nils
中科院分区:
文献类型:
--
作者:
Kawabe, Hiroshi;Neeb, Antje;Dimova, Kalina;Young, Samuel M., Jr.;Takeda, Michiko;Katsurabayashi, Shutaro;Mitkovski, Miso;Malakhova, Oxana A.;Zhang, Dong-Er;Ulmilkawa, Masato;Kariya, Ken-ichi;Goebbels, Sandra;Nave, Klaus-Armin;Rosenmund, Christian;Jahn, Olaf;Rhee, JeongSeop;Brose, Nils
Nedd4-1 is a ‘Neuronal Precursor Cell Expressed and Developmentally Downregulated Protein’ and among the most abundant E3 ubiquitin ligases in mammalian neurons. In analyses of conventional and conditional Nedd4-1 deficient mice, we found that Nedd4-1 plays a critical role in dendrite formation. Nedd4-1, the serine/threonine kinase TNIK, and Rap2A form a complex that controls Nedd4-1-mediated ubiquitination of Rap2A. Ubiquitination by Nedd4-1 inhibits Rap2A function, which reduces the activity of Rap2 effector kinases of the TNIK family and promotes dendrite growth. We conclude that a Nedd4-1/Rap2A/TNIK signaling pathway regulates neurite growth and arborization in mammalian neurons.
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